Bone and other connective tissue generally derive their structure from an extensive matrix structure. Fibrous bundles that are composed of collagen make up the extensive network that provides bone with tension-resistant behavior. Other materials appear in bone matrixes such as proteoglycans, noncollagenous proteins, lipids and acidic proteins. These materials are associated with a mineral phase consisting primarily of hydroxyapatite and the combination of the materials with hydroxyapatite tend to be poorly crystallized. In other words, bone and tooth minerals are impure forms of hydroxyapatite. In general, the crystals of pure synthetic apatites, geological apatites and many impure synthetically produced apatites are larger and more crystalline than the biological crystals of bone, dentin, cementum and cartilage. The crystals of bone, dentin and cementum are very small, irregularly shaped, very thin plates whose rough average dimensions are approximately 10 to 50 angstroms in thickness, 30 to 150 angstroms in width, and 200 to 600 angstroms in length.
When bone undergoes fracture or degradation, bone tissue undergoes remodeling, which is a process that occurs in mammals wherein bone tissue is continuously renewed throughout the life of those mammals. The process of remodeling occurs through the interplay of osteoblasts (bone forming cells) and osteoclasts (a large multinucleate cell found in growing bone that resorbs bony tissue, such as in the formation of canals and cavities).
There are diseases that affect the remodeling of bone such as osteoporosis. Osteoporosis is a systemic disease of the whole organism, which is essentially expressed by an imbalance of bone formation (i.e., the catabolic pathways of the osteoclasts predominates over the metabolic pathway of the osteoblasts). In other words, the anabolic and catabolic bone restructuring processes are reversed, and more bone material is decomposed by an osteoclastic activity, than is grown by the osteoblastic activity.
One means of attempting to control this reversal of bone formation rate is to deliver systemically effective substances. These include, for example, bisphosphonates and hormone preparations, which may aid in accelerating (or at least maintaining) the bone formation rate, but in the process may also lead to adverse side effects at other parts of the patient. Accordingly, to limit the use of these potentially threatening therapies, it is desirable to find bone substitute materials that not only acts as a bone substitute substance or filler, but that also operate upon surrounding bone cells in such a way that it increases and/or induces the metabolic processes (while slowing catabolic processes), so that the excessive osteoclastic activity is attenuated and osteoblastic activity (the in-growth of bones) is increased.
Thus, much research has been performed on developing different bone filling cement formulations to aid in treating bone diseases such as osteoporosis. The use of these bone cement formulations may be used when performing surgery. There are many types of surgery in which bone cement formulations may be used. For example, back surgery, which includes but is not limited to vertebroplasty and/or kyphoplasty, is a type of surgery where bone cement(s) is/are used.
Researchers and physicians have developed cement formulations that contain calcium phosphate. Calcium phosphate is a material that is used in bone cement that is known to enhance the accretion (growth) of bone to a non-biological surface. When bone cements containing calcium phosphate are used as bone void fillers, the calcium phosphates replace living bone through the bone cascade and remodeling process. Although calcium phosphate cement formulations increase accretion, there are instances where it is desirable to further increase accretion to reverse bone catabolism or wherein a bone injury has occurred.
The rate of replacement and resorption in bone is a function of a plurality of factors, including but not limited to the crystallinity of the bone cement formulations as well as its porosity.
The formulations that are presently in use as bone cements may contain either one or the other of the requisite crystallinity or porosity or neither. However, the bone cements that are used for replacement and resorption tend to lack both adequate crystallinity and porosity. That is, the bone cement formulations may have adequate crystallinity but inadequate porosity or may have adequate porosity but inadequate crystallinity. However, to date, bone cements that have both adequate crystallinity and porosity have not yet been developed. Having adequate porosity means having adequate macroscopic pores of varying sizes and densities that allow for efficient bone remodeling. Moreover, having adequate macroscopic pores of varying sizes can increase bone accretion. Without being bound by a particular theory regarding increased porosity, it is believed that increasing surface area of the bone cement formulation may allow osteoblastic cells to better perform their metabolic function. In particular, an increase in variably sized macroscopic pores may result in enhanced accretion. Moreover, without being bound to a particular theory, it is believed that the bony defects that are created by the macroscopic pores also allow blood to better absorb and provide avenues for the entrance of growth factors and BMP (bone morphogenic protein).
Accordingly, bone filling cement with improved crystallinity and/or porosity may be desirable in various medical applications.